The process of restonosis, or renarrowing of an e.g. a coronary artery lumen following a revascularization procedure, most likely begins at the time of percutaneous intervention. Restenosis typically can involve mechanical processes such as elastic recoil, or acute renarrowing of an artery after e.g. balloon angioplasty, and processes such as negative arterial remodeling—as the vessel begins to heat, the outermost vessel layer (the adventitial layer) may shrink inward. Neointimal hyperplasia (NIH), another process in the development of restenosis, is not a mechanical function of the anatomy of an artery, but a biological wound healing response to the injury caused by percutaneous coronary intervention. Neointimal hyperplasia can involve smooth muscle cell proliferation, migrations and/or production of the extracellular matrix. With the introduction of arterial stents, the problems of elastic recoil or negative arterial remodeling has been substantially eliminated. However, neointimal hyperplasia is still a primary cause of restenosis after the introduction of a stent in the artery of a patient. Both bare metal stents and drug-eluting stents that typically elute an anti-restenosis agent are available.
Drug eluting stents are not optimal under all conditions, however. Such stents may not be appropriate for small vessels, and drug eluting stents can hinder vessel healing. For example, drug eluting stents may lead to a higher rate of thrombosis e.g. a year after implantation, when for example antiplatelet therapy (e.g. clopidogrel) is discontinued. For patients needing surgery, for example, patients may suffer fatal heart attacks due to clotting inside of drug-eluting stents, even months or years after surgery, particular if blood thinning medication is stopped (as is often necessary) before surgery. Patients identified as being likely to be non-compliant with antiplatelet therapy may not be suitable candidates for drug-eluting stents.
Therefore, it has been suggested that use of bare metal stents may actually provide a safer choice, at least for some patients. Improved compositions and methods for delivery of anti-neointimal hyperplasia, or anti-restenosis, agents for local and/or targeted delivery to blood vessels, for example, in conjunction with placement of a bare-metal stents is therefore needed.